New Phylogenetic Models Incorporating Interval-Specific Dispersal Dynamics Improve Inference of Disease Spread.

Phylodynamic methods reveal the spatial and temporal dynamics of viral geographic spread, and have featured prominently in studies of the COVID-19 pandemic. Virtually all such studies are based on phylodynamic models that assume-despite direct and compelling evidence to the contrary-that rates of viral geographic dispersal are constant through time. Here, we: (1) extend phylodynamic models to allow both the average and relative rates of viral dispersal to vary independently between pre-specified time intervals; (2) implement methods to infer the number and timing of viral dispersal events between areas; and (3) develop statistics to assess the absolute fit of discrete-geographic phylodynamic models to empirical datasets. We first validate our new methods using simulations, and then apply them to a SARS-CoV-2 dataset from the early phase of the COVID-19 pandemic. We show that: (1) under simulation, failure to accommodate interval-specific variation in the study data will severely bias parameter estimates; (2) in practice, our interval-specific discrete-geographic phylodynamic models can significantly improve the relative and absolute fit to empirical data; and (3) the increased realism of our interval-specific models provides qualitatively different inferences regarding key aspects of the COVID-19 pandemic-revealing significant temporal variation in global viral dispersal rates, viral dispersal routes, and the number of viral dispersal events between areas-and alters interpretations regarding the efficacy of intervention measures to mitigate the pandemic.